Menu
GeneBe

1-153544656-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002961.3(S100A4):c.139G>A(p.Gly47Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

S100A4
NM_002961.3 missense, splice_region

Scores

4
14
Splicing: ADA: 0.002304
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.25
Variant links:
Genes affected
S100A4 (HGNC:10494): (S100 calcium binding protein A4) The protein encoded by this gene is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100 proteins are localized in the cytoplasm and/or nucleus of a wide range of cells, and involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. S100 genes include at least 13 members which are located as a cluster on chromosome 1q21. This protein may function in motility, invasion, and tubulin polymerization. Chromosomal rearrangements and altered expression of this gene have been implicated in tumor metastasis. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3072049).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
S100A4NM_002961.3 linkuse as main transcriptc.139G>A p.Gly47Arg missense_variant, splice_region_variant 2/3 ENST00000368716.9
S100A4NM_019554.3 linkuse as main transcriptc.139G>A p.Gly47Arg missense_variant, splice_region_variant 3/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
S100A4ENST00000368716.9 linkuse as main transcriptc.139G>A p.Gly47Arg missense_variant, splice_region_variant 2/31 NM_002961.3 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 03, 2022The c.139G>A (p.G47R) alteration is located in exon 3 (coding exon 1) of the S100A4 gene. This alteration results from a G to A substitution at nucleotide position 139, causing the glycine (G) at amino acid position 47 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.45
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.55
Cadd
Benign
22
Dann
Uncertain
1.0
DEOGEN2
Benign
0.31
T;T;T;T
Eigen
Benign
-0.085
Eigen_PC
Benign
-0.092
FATHMM_MKL
Benign
0.19
N
M_CAP
Benign
0.026
D
MetaRNN
Benign
0.31
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.5
L;L;L;L
MutationTaster
Benign
0.99
D;D;D;D
PrimateAI
Uncertain
0.58
T
PROVEAN
Uncertain
-4.0
D;D;D;D
REVEL
Benign
0.078
Sift
Benign
0.15
T;T;T;T
Sift4G
Benign
0.15
T;T;T;T
Polyphen
0.71
P;P;P;P
Vest4
0.17
MutPred
0.46
Gain of solvent accessibility (P = 0.0097);Gain of solvent accessibility (P = 0.0097);Gain of solvent accessibility (P = 0.0097);Gain of solvent accessibility (P = 0.0097);
MVP
0.59
MPC
0.36
ClinPred
0.95
D
GERP RS
3.9
Varity_R
0.41
gMVP
0.45

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.0023
dbscSNV1_RF
Benign
0.18
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1005770068; hg19: chr1-153517132; API